title: Identification of HLA ligands and T-cell epitopes for immunotherapy of lung cancer.
abstract: BACKGROUND
  Lung cancer is the most common cancer worldwide. Every year, as many people die of lung cancer as of breast, colon and rectum cancers combined. Because most patients are being diagnosed in advanced, not resectable stages and therefore have a poor prognosis, there is an urgent need for alternative therapies. Since it has been demonstrated that a high number of tumor- and stromal-infiltrating cytotoxic T cells (CTLs) is associated with an increased disease-specific survival in lung cancer patients, it can be assumed that immunotherapy, e.g. peptide vaccines that are able to induce a CTL response against the tumor, might be a promising approach.
  
  
  METHODS
  We analyzed surgically resected lung cancer tissues with respect to HLA class I- and II-presented peptides and gene expression profiles, aiming at the identification of (novel) tumor antigens. In addition, we tested the ability of HLA ligands derived from such antigens to generate a CTL response in healthy donors.
  
  
  RESULTS
  Among 170 HLA ligands characterized, we were able to identify several potential targets for specific CTL recognition and to generate CD8+ T cells which were specific for peptides derived from cyclin D1 or protein-kinase, DNA-activated, catalytic polypeptide and lysed tumor cells loaded with peptide.
  
  
  CONCLUSIONS
  This is the first molecular analysis of HLA class I and II ligands ex vivo from human lung cancer tissues which reveals known and novel tumor antigens able to elicit a CTL response.
authors.affiliation: Department of Immunology, Interfaculty Institute for Cell Biology, University of Tübingen, Auf der Morgenstelle 15, Tübingen, 72076, Germany.
authors.forename: Anneke
authors.initials: A
authors.lastname: Neumann
authors.forename: Helen
authors.initials: H
authors.lastname: Hörzer
authors.forename: Nina
authors.initials: N
authors.lastname: Hillen
authors.forename: Karin
authors.initials: K
authors.lastname: Klingel
authors.forename: Barbara
authors.initials: B
authors.lastname: Schmid-Horch
authors.forename: Hans-Jörg
authors.initials: HJ
authors.lastname: Bühring
authors.forename: Hans-Georg
authors.initials: HG
authors.lastname: Rammensee
authors.forename: Hermann
authors.initials: H
authors.lastname: Aebert
authors.forename: Stefan
authors.initials: S
authors.lastname: Stevanović
mesh_terms: D000595:Amino Acid Sequence; D017951:Antigen Presentation; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D019938:Cyclin D1 / Q000276:immunology; D051747:DNA-Activated Protein Kinase / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D015870:Gene Expression; D006680:HLA Antigens / Q000276:immunology*; D006801:Humans; D007150:Immunohistochemistry; D007167:Immunotherapy; D008024:Ligands; D008175:Lung Neoplasms / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000276:immunology; D010455:Peptides / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
chemical_list: C530104:CCND1 protein, human; D018984:Epitopes, T-Lymphocyte; D006680:HLA Antigens; D008024:Ligands; D009687:Nuclear Proteins; D010455:Peptides; D019938:Cyclin D1; D051747:DNA-Activated Protein Kinase; C497263:PRKDC protein, human